The noninvasive determination of glucose in the interstitial layer of the human skin by mid-infrared spectroscopy is reported. The sensitivity for this measurement was obtained by combining the high pulse energy from an external cavity quantum cascade laser (EC-QCL) tunable in the infrared glucose fingerprint region (1000-1220 cm(-1)) focused on the skin, with a detection of the absorbance process by photoacoustic spectroscopy in the ultrasound region performed by a gas cell coupled to the skin. This combination facilitates a quantitative measurement for concentrations of skin glucose in the range from <50 mg/dL to >300 mg/dL, which is the relevant range for the glucose monitoring in diabetes patients. Since the interstitial fluid glucose level is representative of the blood glucose level and follows it without significant delay (<10 min), this method could be applied to establish a noninvasive, painless glucose measurement procedure that is urgently awaited by diabetes patients. We report here the design of the photoacoustic experiments, the spectroscopy of glucose in vivo, and the calibration method for the quantitative determination of glucose in skin. Finally, a preliminary test with healthy volunteers and volunteers suffering from diabetes mellitus demonstrates the viability of a noninvasive glucose monitoring for patients based on the combination of infrared QCL and photoacoustic detection.

Membrane proteins often form oligomeric complexes within the lipid bilayer, but factors controlling their assembly are hard to predict and experimentally difficult to determine. An understanding of protein-protein interactions within the lipid bilayer is however required in order to elucidate the role of oligomerization for their functional mechanism and stabilization. Here, we demonstrate for the pentameric, heptahelical membrane protein green proteorhodopsin that solid-state NMR could identify specific interactions at the protomer interfaces, if the sensitivity is enhanced by dynamic nuclear polarization. For this purpose, differently labeled protomers have been assembled into the full pentamer complex embedded within the lipid bilayer. We show for this proof of concept that one specific salt bridge determines the formation of pentamers or hexamers. Data are supported by laser-induced liquid bead ion desorption mass spectrometry and by blue native polyacrylamide gel electrophoresis analysis. The presented approach is universally applicable and opens the door toward analyzing membrane protein interactions within homo-oligomers directly in the membrane.

The application of a novel open, windowless cell for the photoacoustic infrared spectroscopy of human skin is described. This windowless cavity is tuned for optimum performance in the ultrasound range between 50 and 60 kHz. In combination with an external cavity tunable quantum cascade laser emitting in the range from ~1000 cm(-1) to 1245 cm(-1), this approach leads to high signal-to-noise-ratio (SNR) for mid-infrared spectra of human skin. This opens the possibility to measure in situ the absorption spectrum of human epidermis in the mid-infrared region at high SNR in a few (~5) seconds. Rapid measurement of skin spectra greatly reduces artifacts arising from movements. As compared to closed resonance cells, the windowless cell exhibits the advantage that the influence of air pressure variations, temperature changes, and air humidity buildup that are caused by the contact of the cell to the skin surface can be minimized. We demonstrate here that this approach can be used for continuous and non-invasive monitoring of the glucose level in human epidermis, and thus may form the basis for a non-invasive monitoring of the glucose level for diabetes patients.

The formation of oligomers of the amyloid-β peptide plays a key role in the onset of Alzheimer's disease. We describe herein the investigation of disease-relevant small amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing functionally relevant structural attributes. In particular we can show that amyloid-β oligomers develop in two distinct arrangements leading to either neurotoxic oligomers and fibrils or non-toxic amorphous aggregates. Comprehending the key-attributes responsible for those pathways on a molecular level is a pre-requisite to specifically target the peptide's tertiary structure with the aim to promote the emergence of non-toxic aggregates. Here we show for two fibril inhibiting ligands, an ionic molecular tweezer and a hydrophobic peptide that despite their different interaction mechanisms, the suppression of the fibril pathway can be deduced from the disappearance of the corresponding structure of the first amyloid-β oligomers.

We present TIR-PTD spectroscopy, an IR-pump/VIS-probe method for the measurement of IR absorption spectra by means of photothermal deflectometry (PTD) enhanced by total internal reflection (TIR). It overcomes the limitations of IR spectroscopy for the study of opaque samples and allows molecular fingerprinting of IR-active liquids or solids. Another important advantage of the presented approach over traditional IR spectroscopy methods is the ability to obtain IR information by means of VIS detection, which is generally much cheaper and easier to handle than IR detection. By application of mid-IR TIR-PTD spectroscopy on human skin in vivo, we are demonstrating the correlation between epidermal- and blood-glucose levels on a type 1 diabetic patient.